RESUMEN
Objective To evaluate the efficacy of high performance liquid chromatography (HPLC) for simultaneous determination of propofol and remifentanil concentrations in human plasma.Methods Methods Eighteen healthy volunteers of both sexes,aged 18-45 yr,weighing 52-81 kg,were enrolled in the study.Venous blood samples were collected,and the concentrations of propofol and remifentanil in human plasma were detected simultaneously by HPLC.The internal standard was thymol.Potassium dihydrogen phosphate 0.1 mol/L was added to the plasma and then the plasma samples were extracted with extract liquor (ethyl acetate ∶ hexane =4 ∶ 1,V/V).The analytical column was ZORBAX Eclipse XDB-C18 (4.6 mm×250 mm,5 μm).The mobile phase was methano ∶ 0.02 mol/L NaH2PO4 ∶ acetonitrile,the flow rate was 1.0 ml/min,the detection wavelength was 210 nm within 1-7 min,and 266 nm within 7-16 min,and the sample size was 20 μl.Linear regression analysis was performed by using the least-squares method.The specimens of the blood with the final concentration of remifentanil 1.00,5.00 and 20.00 ng/ml and propofol 0.50,2.00 and 10.00 μg/ml were obtained to determine the recovery,precision and stability.Results Linear regression equation of remifentanil was C=12.853 5Ai/As+0.084 8 (R2 =0.999 4),and this system showed a good linear relationship with the concentration of remifentanil ranged 0.5-40.0 ng/ml.Linear regression equation of propofol was C=8.554 3 Ai/As+0.029 1 (R2=0.998 6),and this system showed a good linear relationship with the concentration of propofol ranged 0.2-20.0 μg/ml.For both propofol and remifentanil concentrations,the relative recovery was within the range of 85％-115％,the absolute recovery was larger than 75％,and the relative standard deviation of intra-and inter-day precision and stability was less than 5％.The method was proved to meet the requirements of biological sample analysis.Conclusion For HPLC method established in this trial,the determination is sensitive,reproducible,rapid and simple,and it can be used for simultaneous determination of propofol and remifentanil concentrations in human plasma and for clinical pharmacokinetic research.
RESUMEN
Objective To investigate the pharmacokinetics of propofol when combined with remifentanil in patients with liver cirrhosis.Methods Ten patients (5 males, 5 females) with liver cirrhosis scheduled for endoscopic esophageal varix ligation (test group) and 10 cases (5 males, 5 females) with normal liver function scheduled for gastroscopy (control group), aged 18-55 yr, weighing 40-75 kg, were studied. The patients were unpremedicated. All the patients received iv injection of propofol 1.5 mg/kg and remifentanil 0.5 μg/kg, and 5 min later propofol 0.5 mg/kg and remifentanil 0.2 μg/kg was given again. Blood samples were taken from radial artery before administration and at 2, 5, 10, 15, 20, 30, 45, 60, 80 and 120 min after administration for determination of the plasma propofol concentration using gas chromatography-mass spectrography. The pharmacokinetic parameters were calculated using DAS 2.0 software.Results The pharmacokinetics of propofol was best described by a three-compartment open model. There was no significant difference in the distribution half-life, elimination halflife , terminal half-life, area under the curve and transfer rate constant between the two groups ( P ＞ 0.05) . The apparent volume of distribution of propofol and clearance were significantly increased in test group compared with control group (P ＜0.01) .Conclusion When propofol combined with remifentanil is used in patients with liver cirrhosis, the apparent volume of distribution of propofol and clearance are significantly increased, while no changes in the other pharmacokinetic parameters are found.